Kite Pharma Uses CRADAs to Conduct Important Clinical Research on New Cancer Treatments

Kite Pharma, Inc., which is racing Juno Therapeutics and Swiss pharmaceutical giant Novartis to successfully bring the first T-cell receptor (TCR) therapy to market, relies heavily on government support in the course of its research and development.

As noted previously by KEI, in various comments to the National Institutes of Health, the NIH rarely discloses detailed information on its connections with industry, raising concerns about how the NIH licenses out taxpayer-funded technologies without regard for future prices or access for U.S. residents.

T-cell receptor therapy is the latest breakthrough in cancer treatment, and involves modifying a patient's own cells to better track and destroy cancer proteins, and then reintroducing them into the body. (The NIH has a concise description for non-scientists here.)

Dr. Steven A. Rosenberg is the Principal Investigator for the National Cancer Institute on Kite's 2012 CRADA. Dr. Rosenberg mentored Kite CEO and co-Founder Dr. Arie Belldegrun, and is also listed as a "Special Advisor" to Kite on their website. | Partnership for Public Service / Aaron Clamage

According to Kite’s filings with the Securities and Exchange Commission (SEC), Kite has secured three Cooperative Research and Development Agreements (CRADAs) with the National Cancer Institute (NCI). In exchange for quarterly cash payments, the NCI conducts clinical trials and laboratory work on many of its own patented technologies, with the understanding that Kite will have the rights to commercialize any successful products developed through the CRADA.

Kite entered into its first CRADA in 2012, with Dr. Steven A. Rosenberg, the NCI’s Chief of Surgery, as the principal investigator. Dr. Rosenberg, who mentored Kite CEO and co-Founder Arie Belldegrun during his fellowship at the National Cancer Institute, is also listed as a "Special Advisor" to Kite on their website. Under the broad terms of that CRADA, NCI conducts research into various different types of TCR therapies, and Kite pays the NIH $3 million annually.

KEI obtained the first CRADA through Kite’s SEC filings and through FOIA.

The Research Plan abstract describes the general goals and scope of the product:

“The principal goal of this CRADA is to develop and clinically evaluate safe and effective NCI proprietary genetically modified peripheral blood Autologous T Cell Therapy (ACT)/T cell receptor (TCR) products for treating patients with various advanced and metastatic cancer indications, utilizing the development expertise of Kite Pharma, Inc. (“Kite”). These ACT/TCR products consist of autologous peripheral blood lymphocytes genetically modified to express NCI proprietary T cell receptors (TCRs) or NCI proprietary chimeric antigen receptors (CARs) that target the patient’s tumor cells (for the purposes of this Agreement, TCR will refer to TCR and/or CAR interchangeably). Specifically this CRADA will support 1) evaluation of the clinical safety and efficacy of current and future NCI proprietary ACT/TCR products in relevant cancer indications and the development of optimized clinical and product protocols to be conducted by NCI; 2) optimization of ACT/TCR product manufacturing and characterization in compliance with cGMP, suitable for large multi-center trials and commercialization processes to broad patient populations; 3) generation and advancement to phase I/IIa clinical trials of additional ACT/TCR products, and the development of technologies to enhance ACT/TCR product potency and durability of clinical response.”

The NIH withheld the research plan in full, as did Kite in its SEC filings, under confidentiality provisions.

While the NIH also withheld the “background” intellectual property — technologies for which the NIH has already obtained a patent or applied for one — Kite disclosed a portion of that IP in its SEC filings (see pages 37-38 here). Kite licensed at least two of the background inventions (PCT/US2011/051537 and PCT/US2012/029861) from the NIH in April 2013.

Kite described the 2012 CRADA as particularly important for their pipeline in its annual SEC filing for 2015: “A substantial portion of our research and development has been conducted by the NCI under the CRADA entered into in August 2012.”

The company’s most promising technology, KTE-C19, is a Chimeric-Antigen Receptor T-cell (CAR-T) therapy that is currently in phase 2 testing for mantle cell lymphoma, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma. Kite is also testing KTE-C19 for adult & pediatric acute lymphoblastic leukemia, chronic lymphocytic leukemia, and follicular lymphoma, as well as for heme malignancies and solid tumors in joint studies with Amgen.

In January 2016, Kite entered into a narrower CRADA for NCI to conduct clinical evaluations on KTE-C19, costing $2.5 million total for Kite over the course of the Agreement. According to the CRADA:

“The National Cancer Institute and Kite Pharma, Inc. have entered into a Cooperative Research and Development Agreement (CRADA) to: 1) evaluate an NCI-developed monomeric chimeric antigen receptor (CAR) targeting CD19 for the treatment of B cell lymphoma and B cell leukemia, and 2) pursue the development of novel CARs for the treatment of B cell lymphoma and B cell leukemia.”

Finally, in June 2016, Kite entered into a CRADA to pursue clinical development on “T-cell receptor (TCR) product candidates directed against human papillomavirus (HPV)-16 E6 and E7 oncoproteins for the treatment of HPV-associated cancers,” according to a Kite press release.

The 2012 and January 2016 CRADAs are available as PDFs at the end of this blog post, and were obtained by KEI through FOIA.

In addition to its CRADAs, Kite has executed at least six exclusive patent licensing agreements with the NIH, covering at least 14 international and national patent applications, for which at least 2 patents have been granted in the United States. The patents cover a wide range of technologies related to various TCR therapies for different cancer types, including lymphomas and leukemias, cervical, and head & neck cancers. Kite will have worldwide rights to exclusively market all of those products upon successful commercialization.

Currently, Kite is in negotiations with the NIH to execute a sixth license covering two additional inventions related to a CAR-T therapy targeted towards CD70-expressing cancers.